Rates of Alterations across Melanoma Subtypes and a Complete Response to Trastuzumab Emtansine in an -Amplified Acral Melanoma.

Purpose: Patients with V600 wild-type melanoma whose tumors progress on checkpoint inhibition currently have limited therapeutic options, and additional rational treatment targets are needed. alterations may be amenable to targeted inhibition, but the rate of alterations across melanoma subtypes is not well described.

Patients And Methods: All patients with nonuveal melanoma (cutaneous, acral, mucosal, and unknown primary) whose tumors underwent multigene sequencing with MSK-IMPACT at Memorial Sloan Kettering Cancer Center (New York, NY) from 2014 to 2018 were reviewed for known or likely oncogenic somatic alterations in and the other known canonical driver genes , and .

Results: A patient with acral melanoma resistant to checkpoint inhibition was found to have amplification and achieved a durable complete response to trastuzumab emtansine. Tumor sequencing results from 732 melanoma cases were analyzed for and canonical driver gene alterations. ERBB2 amplifications were detected in acral (3%) and mucosal (3%) melanomas. mutations were found in cutaneous (1%), acral (2%), and mucosal (2%) subtypes and frequently cooccurred with alterations. Among the 140 patients whose tumors lacked canonical driver alterations, amplifications were detected in acral (7%) and mucosal (6%) melanomas.

Conclusions: amplification is present in a minority of acral lentiginous and mucosal melanomas. Activating mutations in were identified in nonuveal melanoma subtypes and are frequently comutated with canonical drivers. HER2 could represent a therapeutically relevant target across melanoma subtypes.